Angiotensin II-superoxide-NFκB signaling and aortic baroreceptor dysfunction in chronic heart failure.
Angiotensin II-superoxide-NFκB signaling and aortic baroreceptor dysfunction in chronic heart failure.
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DOI：
10.3389/fnins.2015.00382
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发表时间：
2015
影响因子：
4.3
通讯作者：
Li YL
中科院分区：
文献类型：
--
作者：
Zhang D;Muelleman RL;Li YL
慢性心力衰竭 (CHF) 影响着美国约 570 万人。越来越多的临床和实验研究证据表明，动脉压力反射的敏感性在 CHF 状态下减弱，这是心源性猝死的预测危险因素。通常，动脉压力感受反射通过主动脉弓和颈动脉窦中的压力感受器末梢感知动脉血管壁的机械变化来调节血压和心率。结状神经节（NG）中有主动脉压力感受器神经元，是动脉压力感受反射的主要传入成分。压力感受器神经元的功能变化与 CHF 的动脉压力感受反射功能障碍有关。在 CHF 状态下，NG 中循环血管紧张素 II (Ang II) 和局部 Ang II 浓度升高，AT1R mRNA 和蛋白在 NG 中过度表达。此外，Ang II-超氧化物-NFκB信号通路通过影响主动脉压力感受器Nav通道的表达和激活来调节主动脉压力感受器的神经元兴奋性，从而导致CHF中动脉压力感受性反射的损害。这些新发现为改善 CHF 状态下动脉压力感受反射敏感性的潜在药物干预措施提供了基础。本综述总结了 CHF 动脉压力感受反射功能障碍的机制。
Chronic heart failure (CHF) affects approximately 5.7 million people in the United States. Increasing evidence from both clinical and experimental studies indicates that the sensitivity of arterial baroreflex is blunted in the CHF state, which is a predictive risk factor for sudden cardiac death. Normally, the arterial baroreflex regulates blood pressure and heart rate through sensing mechanical alteration of arterial vascular walls by baroreceptor terminals in the aortic arch and carotid sinus. There are aortic baroreceptor neurons in the nodose ganglion (NG), which serve as the main afferent component of the arterial baroreflex. Functional changes of baroreceptor neurons are involved in the arterial baroreflex dysfunction in CHF. In the CHF state, circulating angiotensin II (Ang II) and local Ang II concentration in the NG are elevated, and AT1R mRNA and protein are overexpressed in the NG. Additionally, Ang II-superoxide-NFκB signaling pathway regulates the neuronal excitability of aortic baroreceptors through influencing the expression and activation of Nav channels in aortic baroreceptors, and subsequently causes the impairment of the arterial baroreflex in CHF. These new findings provide a basis for potential pharmacological interventions for the improvement of the arterial baroreflex sensitivity in the CHF state. This review summarizes the mechanisms responsible for the arterial baroreflex dysfunction in CHF.